Correlation between serum microRNA-124-3p and silent information regulator 1 levels in type 2 diabetic patients with different stages of diabetic kidney disease

Objective To investigate changes of serum microRNA(Mir)-124-3p and silent information regulator 1(Sirt1) levels in type 2 diabetic patients with different stages of diabetic nephropathy. Methods Total of 508 cases with type 2 diabetes treated from September 2013 to September 2015 were divided into three groups according to the urinary albumin excretion rate: normoalbuminuric(D1, n=193), microalbuminuric(D2, n=175), macroalbuminuric group(D3, n=140). Serum levels of Mir-124-3p were validated by real-time polymerase chain reaction. Serum Sirt1, hypoxia-inducible factor-1α(HIF-1α), tumor necrosis factor-α(TNF-α) and fibronectin(FN) were determined by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance, Pearson correlation and multiple stepwise regression analysis were used for statistical analysis. Results The level of serum Mir-124-3p in type 2 diabetic patients (2.85 (2.78-2.92)ng/mg) was significantly higher than that in control group (0.91(0.87-0.95)ng/mg), and with the increase of urinary albumin excretion rate, the levels of serum Mir-124-3p in group D1, D2 and D3 increased gradually(F=1348.7, P<0.001). Compared with control, serum Sirt1 level decreased significantly in type 2 diabetic patients and decreased gradually in patients of D1, D2 and D3 groups(F=44.5, P<0.001). According to Pearson correlation analysis, age, diabetes duration, fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance(HOMA-IR), glycated hemoglobin A1c(HbA1c), low-density lipoprotein-cholesterol(LDL-C), total cholesterol(TC), triglyceride(TG), serum creatinine(Scr), blood urea nitrogen(BUN), uric acid(UA), HIF-1α, Mir-124-3p, FN and TNF-α were positively correlated with Ln(ACR) (r=0.105-0.813, P<0.05); high-density lipoprotein-cholesterol(HDL-C) and Sirt1 were negatively correlated with Ln(ACR) (r=-0.113,-0.360, both P<0.05). According to multiple stepwise regression analysis, Mir-124-3p, FN, TNF-α, HIF-1α, TC, diabetes duration, BUN, Sirt1, UA and age were independent factors that significantly influenced Ln(ACR), the equation was Ln(ACR)=-3.617+1.005×Mir-124-3p+0.002×FN+ 0.014×TNF-α+0.035×HIF-1α+0.131×TC+0.016×diabetes duration+0.148×BUN-0.031×Sirt1+0.001×UA+ 0.008 × age. Conclusion Serum Mir-124-3p may be a new biomarker of early diagnosis of diabetic nephropathy, and it may involve in the development of diabetic nephropathy by promoting chronic inflammatory reaction and renal fibrosis. Key words: Diabetes mellitus, type 2; Diabetic nephropathies; MicroRNA-124-3p; Silent information regulator 1; Hypoxia-inducible factor-1α